Formulations of a transdermal patch for pain management

This patent application claims priority to U.S. Provisional Patent Application Ser. No. 62/603,388 entitled “FORMULATIONS OF A TRANSDERMAL PATCH FOR PAIN MANAGEMENT”, filed on May 30, 2017.

Chronic pain represents an emerging public health issue of massive proportions, particularly in view of aging populations in industrialized nations. About 19% of adults (about 38 million) in USA have chronic pain.

The present application discloses various compositions (as listed below) of bioactive compounds of a pressure sensitive transdermal patch (e.g., a pressure sensitive single-layer transdermal/multi-layer/reservoir transdermal patch) for pain management. Among the benefits of a pressure sensitive transdermal patch are reduced gastro-intestinal incompatibility, steady dosage rate/flux rate, self-administration and non-invasive procedure.

Pressure Sensitive Single-Layer Transdermal Patch: The adhesive layer of the pressure sensitive single-layer transdermal patch contains bioactive compounds. The adhesive layer not only adheres with the various layers together, along with the entire system to the skin, but also is responsible for the releasing of the bioactive compounds. The adhesive layer is surrounded by a temporary liner and a backing.

Pressure Sensitive Multi-Layer Transdermal Patch: One of the layers of the pressure sensitive multi-layer transdermal patch is for immediate release of bioactive compounds and other layer is for control release of the bioactive compounds from an embedded reservoir. It has both a temporary liner-layer and a permanent backing. The release of the bioactive compounds depends on membrane permeability and diffusion of drug molecules.

Pressure Sensitive Reservoir Transdermal Patch: Unlike the pressure sensitive single-layer transdermal patch and pressure sensitive multi-layer transdermal patch, the pressure sensitive reservoir transdermal patch has a separate layer of bioactive compounds in solution or suspension (separated by an adhesive layer). The reservoir of the bioactive compounds is encapsulated in a shallow compartment, which molded from a bioactives-impermeable metallic plastic laminate with rate-controlling polymer (e.g., vinyl acetate) membrane on one surface. This patch is also backed by the backing layer.

The adhesive (e.g., polyacrylates, polyisobutylene or silicon based adhesive) of the pressure sensitive single-layer transdermal/multi-layer plays a critical role for establishing (a) flux rate of the bioactive compounds to skin, (b) adhesion to skin, (c) stability/shelf life, (d) peel strength and (e) skin irritation.

Furthermore, a patch can utilize low-level electrical energy to transport bioactive compounds through the skin in a controlled manner.

Additionally, an array of micro-needles located on the surface of a pressure sensitive transdermal patch that comes in contact with the skin can be utilized to deliver bioactive compounds.

Cannabidiol (CBD), a bioactive compound of marijuana plant ( Cannabis sativa or Cannabis indica or its synthetic analogue) or its prodrug can blunt beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression.

Cannabichromene (CBC), a bioactive compound of marijuana plant ( Cannabis sativa or Cannabis indica ). Its molecular structure is described below.

THC content in CBD or CBC is below the federally approved legal limit.

Weight % of the bioactive compound(s) in the pharmaceutical formulations of Table-1 through Table-56 can vary +/−20%

To increase permeation the bioactive compound(s) in the pharmaceutical formulations of Table-1 through Table-56, wherein the bioactive compound(s) in the pharmaceutical formulations of Table-1 through Table-56 is embedded with an adhesive (of a pressure sensitive transdermal patch), a permeation enhancement compound (e.g., oleic acid/eucalyptol oil) can be utilized, a passive compound in the pharmaceutical formulations of Table-1 through Table-56

To reduce chemical reaction between bioactive compounds in the pharmaceutical formulations of Table-1 through Table-56, lecithin (e.g., soy-derived lecithin) a multi-segmented transdermal patch can be utilized instead of a single segmented patch, wherein each segment of the multi-segmented transdermal patch can include one or more compatible bioactive compounds.

To reduce chemical reaction between bioactive compounds in the pharmaceutical formulations of Table-1 through Table-56, lecithin (e.g., soy-derived lecithin) in Table-1 through Table-56 can be utilized.

To increase bioavailability the bioactive compound(s) in the pharmaceutical formulations of Table-1 through Table-56, a microemulsion/nanoemulsion of the bioactive compound(s) in Table-1 through Table-56 can be utilized.

To increase bioavailability the bioactive compound(s) in the pharmaceutical formulations of Table-1 through Table-56, a microencapsulation/nanoencapsulation of the bioactive compound(s) in the pharmaceutical formulations of Table-1 through Table-56 can be utilized.

For sustained delivery of the bioactive compound(s) in the pharmaceutical formulations of Table-1 through Table-56, a microencapsulation/nanoencapsulation of the bioactive compound(s) in the pharmaceutical formulations of Table-1 through Table-56 can be utilized.

For controlled delivery of the bioactive compound(s) in the pharmaceutical formulations of Table-1 through Table-56, a microencapsulation/nanoencapsulation of the bioactive compound(s) in the pharmaceutical formulations of Table-1 through Table-56 can be utilized.

By way of an example and not by way of any limitation, the nanoshell can be a boron nitride nanotube, carbon nanotube, Cornell-dot, cubisome, dendrimer (including plant based dendrimer), deoxyribonucleic acid (DNA) origami nanostructure, exosome, fullerene C 60 (e.g., malonic acid derivative of C 60 ), gold nanoparticles (suitably coated), grapefruit-derived nanovector (GNV), hollow magnetic cage molecule (e.g., Co 12 C 6 , Mn 12 C 6 and Mn 24 C 18 ), iron nanoparticle, lipidoid, liposome, mesoporous silica, micelle, nanocrystal, niosome, polysebacic acid (PSA), polysilsesquioxane (PSQ), porous silicon photonic crystal, quantum dot, quantum dot capped with glutathione, ribonucleic acid (RNA) origami nanostructure, self-assembling peptide (or self-assembling protein), solid-lipid nanoparticle, spherical nucleic acid (SNA), synthasome, tubular/tetrahedral structure fabricated/constructed, utilizing DNA/RNA origami process, virus (e.g., tobacco mosaic virus), zein-plant protein and zeolite-1-nanocrystal.

Silk fibroin is biodegradable and biocompatible. For sustained delivery of the bioactive compound(s) in the pharmaceutical formulations of Table-1 through Table-56, the bioactive compound(s) and/or the pharmaceutical formulations of Table-1 through Table-56 can be loaded with silk fibroin.

In the above disclosed specifications “/” has been used to indicate an “or”.

Any example in the above disclosed specifications is by way of an example only and not by way of any limitation. The best mode requirement “requires an inventor to disclose the best mode contemplated by him/her, as of the time he/she executes the application, of carrying out the invention.” “ . . . [T]he existence of a best mode is a purely subjective matter depending upon what the inventor actually believed at the time the application was filed.” See Bayer AG v. Schein Pharmaceuticals, Inc. The best mode requirement still exists under the America Invents Act (AIA). At the time of the invention, the inventor described preferred best mode embodiments of the present invention. The sole purpose of the best mode requirement is to restrain the inventor from applying for a patent, while at the same time concealing from the public preferred embodiments of their inventions, which they have in fact conceived. The best mode inquiry focuses on the inventor's state of mind at the time he/she filed the patent application, raising a subjective factual question. The specificity of disclosure required to comply with the best mode requirement must be determined by the knowledge of facts within the possession of the inventor at the time of filing the patent application. See Glaxo, Inc. v. Novopharm LTD., 52 F.3d 1043, 1050 (Fed. Cir. 1995).

The above disclosed specifications are the preferred best mode embodiments of the present invention. However, they are not intended to be limited only to the preferred best mode embodiments of the present invention. Numerous variations and/or modifications are possible within the scope of the present invention. Accordingly, the disclosed preferred best mode embodiments are to be construed as illustrative only. Those who are skilled in the art can make various variations and/or modifications without departing from the scope and spirit of this invention. The inventor of the present invention is not required to describe each and every conceivable and possible future embodiment in the preferred best mode embodiments of the present invention. See SRI Int'l v. Matsushita Elec. Corp. of America, 775F.2d 1107, 1121, 227 U.S.P.Q. (BNA) 577, 585 (Fed. Cir. 1985) (enbanc).